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- Obiltoxaximab (Anthim) for inhalation anthrax. [Review]
- MLMed Lett Drugs Ther 2018 Sep 10; 60(1555):150-151
- Drugs and Lactation Database (LactMed): Obiltoxaximab [BOOK]
- BOOKNational Library of Medicine (US): Bethesda (MD)
- No information is available on the clinical use of obiltoxaximab during breastfeeding. Because obiltoxaximab is a large protein molecule with a molecular weight of 148,000, absorption by the infant i…
No information is available on the clinical use of obiltoxaximab during breastfeeding. Because obiltoxaximab is a large protein molecule with a molecular weight of 148,000, absorption by the infant is unlikely after the first few weeks postpartum, and it will probably be destroyed in the infant's gastrointestinal tract. Until more data become available, obiltoxaximab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant.
- Development of Protective Immunity in New Zealand White Rabbits Challenged with Bacillus anthracis Spores and Treated with Antibiotics and Obiltoxaximab, a Monoclonal Antibody against Protective Antigen. [Journal Article]
- AAAntimicrob Agents Chemother 2018; 62(2)
- The recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax protective …
The recommended management of inhalational anthrax, a high-priority bioterrorist threat, includes antibiotics and antitoxins. Obiltoxaximab, a chimeric monoclonal antibody against anthrax protective antigen (PA), is licensed under the U.S. Food and Drug Administration's (FDA's) Animal Rule for the treatment of inhalational anthrax. Because of spore latency, disease reemergence after treatment cessation is a concern, and there is a need to understand the development of endogenous protective immune responses following antitoxin-containing anthrax treatment regimens. Here, acquired protective immunity was examined in New Zealand White (NZW) rabbits challenged with a targeted lethal dose of Bacillus anthracis spores and treated with antibiotics, obiltoxaximab, or a combination of both. Survivors of the primary challenge were rechallenged 9 months later and monitored for survival. Survival rates after primary and rechallenge for controls and animals treated with obiltoxaximab, levofloxacin, or a combination of both were 0, 65, 100, and 95%, and 0, 100, 95, and 89%, respectively. All surviving immune animals had circulating antibodies to PA and serum toxin-neutralizing titers prior to rechallenge. Following rechallenge, systemic bacteremia and toxemia were not detected in most animals, and the levels of circulating anti-PA IgG titers increased starting at 5 days postrechallenge. We conclude that treatment with obiltoxaximab, alone or combined with antibiotics, significantly improves the survival of rabbits that received a lethal inhalation B. anthracis spore challenge dose and does not interfere with the development of immunity. Survivors of primary challenge are protected against reexposure, have rare incidents of systemic bacteremia and toxemia, and have evidence of an anamnestic response.
- Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans. [Journal Article]
- CPClin Pharmacol Drug Dev 2018; 7(6):652-660
- Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillu…
Inhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high-affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6-9 days, and terminal half-life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection-site abscesses or hypersensitivity reactions occurred; no subjects developed treatment-emergent antitherapeutic antibodies over the study period of 71 days.
- New Drugs 2017, part 3. [Journal Article]
- NNursing 2017; 47(11):26-32
- Obiltoxaximab: Adding to the Treatment Arsenal for Bacillus anthracis Infection. [Review]
- APAnn Pharmacother 2017; 51(10):908-913
- CONCLUSIONS: Based on these clinical studies and the implausibility of conducting a trial in infected individuals, obiltoxaximab is a safe and efficacious addition to the anthrax antitoxin armamentarium to protect against and treat inhalational anthrax.
- Animal-to-Human Dose Translation of Obiltoxaximab for Treatment of Inhalational Anthrax Under the US FDA Animal Rule. [Journal Article]
- CTClin Transl Sci 2017; 10(1):12-19
- Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose w…
Obiltoxaximab, a monoclonal antibody against protective antigen (PA), is approved for treatment of inhalational anthrax under the US Food and Drug Administration's (FDA) Animal Rule. The human dose was selected and justified by comparing observed obiltoxaximab exposures in healthy and infected New Zealand White rabbits and cynomolgus macaques to observed exposures in healthy humans, to simulated exposures in healthy and infected humans, and to serum PA levels in infected animals. In humans, at 16 mg/kg intravenous, obiltoxaximab AUC was >2 times that in animals, while maximum serum concentrations were comparable to those in animals and were maintained in excess of the concentration required for PA neutralization in infected animals for 2-3 weeks. Obiltoxaximab 16 mg/kg in humans provided exposure beyond that of 16 mg/kg in animals, ensuring a sufficient duration of PA neutralization to allow for adaptive immunity development. Our approach to dose translation may be applicable to other agents being developed under the Animal Rule.
- Alternative pre-approved and novel therapies for the treatment of anthrax. [Review]
- BIBMC Infect Dis 2016 Nov 03; 16(1):621
- CONCLUSIONS: Several novel and pre-existing antibiotics, as well as toxin inhibitors, have shown increasing promise. A combination treatment that targets both bacterial growth and toxin production would be ideal and probably necessary for effectively combatting this armed bacterium.
- Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies. [Randomized Controlled Trial]
- CTClin Ther 2016; 38(9):2083-2097.e7
- This report describes the safety, immunogenicity, and pharmacokinetic results of obiltoxaximab treatment in healthy subjects from 5 clinical trials.
This report describes the safety, immunogenicity, and pharmacokinetic results of obiltoxaximab treatment in healthy subjects from 5 clinical trials.
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- Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity. [Journal Article]
- AAAntimicrob Agents Chemother 2016; 60(10):5787-95
- Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclona…
Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltoxaximab monotherapy neutralized PA and increased survival across the range of disease severity, indicating clinical benefit of toxin neutralization with obiltoxaximab in both early and late stages of inhalational anthrax.